Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation. 相似文献
OBJECTIVE Despite regular transfusion and desferoxamine treatment, growth failure Is commonly seen In adolescent children with β-thalassaemla major. The growth failure has been thought to be due to GH resistance rather than GH deficiency. We Investigated the effect of GH on short non-GH deficient children with β-thalassaemia. DESIGN Recombinant human GH was given In a dose of 0-14IU/kg/day subcutaneously in an open study. PATIENTS Fifteen prepubertal Chinese children with β-thalassaemia major (ranging from 7.16 to 14.7 years In age) with height ?1.5 SD or more below the population mean for age and a growth velocity of less than 5 cm/year were treated with growth hormone for one year. All children had peak GH response >15mlU/l to insulin Induced hypoglycaemia and normal thyroid function and adrenal reserve. MEASUREMENTS Anthropometric measurements were performed every 3 months. Morning urine was tested twice weekly for glycosuria. Blood count, renal and liver function tests, fasting blood glucose, IGF-I and fructosa-mine levels were assessed at entry and every 3 months during treatment. Fasting Insulin was measured before and after 3 and 12 months of GH treatment. Skeletal maturity was assessed before and after one year of treatment. RESULTS Treatment was stopped in two children after 6 months because of poor growth response and noncompliance with treatment and In one child at 9 months because of bone marrow transplantation. In the 13 children, the growth velocity increased from 3.6±0.7 cm/year to 8±1.2 cm/year after one year of GH treatment (P<0.001). IGF-I was low before treatment (10.1±2.7nmol/l), rising significantly to 15.8±4.8, 18.4±4.6, 19.3±6.4 and 21.9±7.5nmol/l at 3, 6, 9 and 12 months of treatment (P<0.005). The mean pretreatment bone age in the 13 children was 9.58±1.41 years and increased to 10.53±1.43 years after one year of treatment (ΔBA/CA 0.95±0.3 years). None of the patients developed glycosuria or hypertension. There was no significant change in blood count, renal and liver function, thyroid function, fasting blood glucose or insulin concentrations during treatment. CONCLUSION Growth failure In these children with normal GH reserve and low serum IGF-I concentrations would suggest GH insensltlvity. Supraphyslologlcal doses of exogenous GH can cause a significant increase In serum IGF-I levels and a significant Improvement in short-term growth of short children with β-thalassaemia major. 相似文献
OBJECTIVE—To determine whether the β blocker esmolol reduces coronary artery wall stress more than the short acting dihydropyridine calcium antagonist nicardipine. DESIGN—Randomised double blind placebo controlled trial. SETTING—Tertiary cardiology centre. PATIENTS—Patients with coronary artery disease. INTERVENTIONS—20 patients were randomised double blind to an infusion of nicardipine (n = 10) or esmolol (n = 10) titrated to reduce systolic blood pressure by 20 mm Hg. MAIN OUTCOME MEASURES—Peak systolic wall circumferential stress. RESULTS—Esmolol reduced peak coronary stress by a mean of 0.17 × 106 dyn/cm2 (95% confidence interval (CI) 0.14 to 0.21 × 106 dyn/cm2) compared with a reduction of 0.07 × 106 dyn/cm2 (95% CI 0.05 to 0.10 × 106 dyn/cm2) after nicardipine. Peak systolic radius was reduced by 0.04 mm (95% CI 0.03 to 0.06 mm) after esmolol compared with an increase of 0.08 mm (95% CI 0.05 to 0.10 mm) after nicardipine. Heart rate increased by 11.5 beats/min (95% CI 6.9 to 16.2 beats/min) after nicardipine and decreased by 5.3 beats/min (95% CI 1.9 to 8.6beats/min) after esmolol. CONCLUSIONS—Intravenous esmolol is more effective than nicardipine at reducing circumferential coronary artery wall stress.
We assessed the acute haemodynamic effects of dopexamine 1 microgram/kg/min and 3 micrograms/kg/min in 21 patients with coronary arterial disease following routine catheterisation. Patients were aged 38 to 72 years and left ventricular ejection fraction ranged from 23 to 79%. Dopexamine was well tolerated in all patients except one in whom transient ventricular arrhythmias occurred with 3 micrograms/kg/min. No patient developed angina. Dopexamine increased cardiac index (2.6 +/- 0.4 to 3.2 +/- 0.1 (P less than 0.001) and 4.0 +/- 1.0 1/min/m2 (P less than 0.001), control to 1 microgram/kg/min and 3 micrograms/kg/min, respectively) and decreased systemic vascular resistance index (3356 +/- 1506 to 2318 +/- 809 (P less than 0.001) and 2252 +/- 1973 dyne.sec.cm-5/m2 (P less than 0.001], but did not affect systemic arterial, pulmonary arterial or right atrial pressure. Maximum positive dP/dt was increased (1294 +/- 324 to 1597 +/- 505 (P less than 0.001) and 2199 +/- 819 mmHg/sec (P less than 0.001] as was left ventricular stroke work index (44 +/- 20 to 51 +/- 21 (P less than 0.05) and 56 +/- 27 g.m/m2 (P less than 0.001) control to 1 microgram/kg/min and 3 micrograms/kg/min, respectively). Left ventricular end diastolic pressure fell with 3 micrograms/kg/min from 19.8 +/- 6.9 to 12.4 +/- 4.6 mmHg (P less than 0.05) in patients with preserved left ventricular ejection fraction (greater than 50%, n = 6), but not in those with impaired left ventricular ejection fraction (less than 50%, n = 15), otherwise the effects in these two subgroups were similar. We conclude that dopexamine has both inotropic and vasodilator properties.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
PURPOSE The probability of colorectal cancer is moderately increased among carriers of the APC I1307K polymorphism. However, it is not known if endoscopic surveillance of this high-risk group is warranted. The prevalence
of polyps and adenomas in specimens of colorectal cancer who are carriers and noncarriers of the APC I1307K polymorphism is compared.
METHOD Prevalence of adenomatous polyps in the pathology specimens of the study participants, stratified by their APC I1307K polymorphism status, was studied in 900 consecutive cases of colorectal cancer diagnosed in northern Israel between
1998 and 2002, within the framework of a population-based, case-controlled study (MECC Study).
RESULTS The APC I1307K mutation was detected in 78 colorectal cancer cases (8.7 percent) of the study population. Prevalence was higher among
Ashkenazi Jews (11.2 percent) than among non-Ashkenazi Jews (2.7 percent) or Arabs (3.1 percent). After adjustment for age,
APC I1307K carriers were significantly more likely than noncarriers to have polyps in their surgical specimen (51.3 percent vs. 32.6 percent, P = 0.002). Adenomas with a tubular component (either tubular adenomas or tubulovillous adenomas), but not villous adenomas,
were significantly more frequent among carriers (37.2 percent vs. 23.6 percent, P = 0.005).
CONCLUSION Together with former evidence of I1307K being a risk factor for colorectal cancer, these data suggest that colonoscopic surveillance
for colorectal adenomas and cancer may be warranted in I1307K carriers, even in the absence of other identifiable risk factors.
Supported by the National Institutes of Health grant RO1-CA81488 to S.B.G. and G.R. 相似文献
The 9p21 locus has been deleted at a high frequency in a wide variety of tumors. Recently, two genes, p16INK4A and p15INK4B (also called MTS1 and MTS2), have been localized in close proximity at the 9p21 locus, encoding cyclin-dependent kinases 4/6 inhibitors of relative molecular mass 16 kD and 15 kD, respectively and also found to be deleted at a high frequency in tumor cell lines. We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses. The ALL cases showed a relatively high frequency of homozygous deletions (22%, 6 of 27) at the p16INK4A gene locus. Interestingly, of the six cases with p16INK4A homozygous deletions, only three showed homozygous deletions at the p15INK4B gene. In 81 CLL patients, we detected one homozygous and five heterozygous deletions at both the p16INK4A and p15INK4B genes and two heterozygous deletions at the p16INK4A gene alone. Deletion of these two genes in AML cases is relatively low (9%). We did not detect deletions in any of the MDS, HCL, and CML cases examined. Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases. The data presented in this report showed that (1) p16INK4A and p15INK4B genes are preferentially deleted homozygously in ALL and heterozygously in CLL cases with frequent mutation in the second allele, and (2) p16INK4A gene appears to be more frequently deleted than p15INK4B gene. 相似文献
The oxidative burst is likely the most rapid defense response mounted by a plant under pathogen attack, and the generated oxidant species may be essential to several subsequent defense responses. In our effort to characterize the signal-transduction pathways leading to rapid H2O2/O2- biosynthesis, we have examined the role of protein phosphorylation in this resistance mechanism. K-252a and staurosporine, two protein-kinase inhibitors, were found to block the oxidative burst in a concentration-dependent manner. When added during H2O2 generation, the burst was observed to rapidly terminate, suggesting that continuous phosphorylation was essential for its maintenance. Importantly, phosphatase inhibitors (calyculin A and okadaic acid) were found to induce the oxidative burst in the absence of any additional stimulus. This may suggest that certain kinases required for the burst are constitutively active and that stabilization of the phosphorylated forms of their substrates is all that is required for burst activity. In autoradiographs of elicited and unstimulated cells equilibrated with 32PO4(3-), several phosphorylated polypeptide bands were revealed that could represent proteins essential for the burst. 相似文献
A perceived increase in the number of isolates of Moraxella catarrhalis from the respiratory secretions of patients intubated in the pediatric intensive care unit prompted a review of the clinical profiles of such patients and restriction enzyme analysis of the strains involved. Over two months, of 192 patients admitted to the unit, 154 were intubated. Of the 46 for whom endotracheal tube specimens were submitted to the laboratory, M catarrhalis was isolated in 12. M catarrhalis was not felt to be a significant respiratory pathogen by the attending medical staff in any of the patients from whom it was isolated. In only two patients (17%) could nosocomial acquisition be firmly invoked. Restriction enzyme analysis of the 12 strains ruled out the presence of an epidemic strain. Isolation of M catarrhalis from intubated children does not necessarily imply pathogenicity nor an outbreak situation. 相似文献
Background Population screening for osteoporosis using bone mineral density scan is not feasible in Malaysia as this test is costly. Hence, there is a need to develop a more efficient method to screen for osteoporosis.Objectives To determine the feasibility of an interprofessional collaborative osteoporosis screening programme (IPC-OSP). Methods Postmenopausal women aged?≥?50 years, who had not been diagnosed with osteoporosis were recruited from a primary care clinic from June to August 2014. Patients were assessed for their osteoporosis risk and were counselled on prevention methods. Patients at risk were referred to the doctor with a recommendation for a bone mineral density (BMD) scan. Results Fifty out of 55 patients were recruited (response rate?=?90.9%). A total 26/50 (52.0%) went for a bone mineral density scan, none were osteoporotic, 17/50 (34%) were osteopenic, 2/50 (4.0%), were started on osteoporosis medications and 14/50 (28%) modified their lifestyle to improve bone health or started on calcium supplements. Osteoporosis knowledge significantly increased from baseline to month two (46.3?±?21.4 vs. 79.1?±?14.3, p?<?0.001). Patients had a satisfaction score of 89.8?±?12.4. Follow-up rates were 83.9% and 100% at months 1 (BMD appointment) and 2 (phone follow up), respectively. The intervention was successfully coordinated. Data entry was determined to be viable based on the researchers’ experience. Conclusion The interprofessional collaborative osteoporosis screening programme was found to be feasible in Malaysia.